The primary role of the chemistry department at the CTRC Research Foundation is the synthesis and analysis of new chemotherapeutic analogs for in vitro and in vivo evaluation. The chemistry laboratories have all of the personnel, equipment and facilities necessary to fulfill the requirements of this core. The Chemistry Core will synthesize compounds including oligonucleotides, nucleosides/nucleotides, and non-nucleoside reverse transcriptase inhibitors to determine structure-activity relationships for Program 1. The Chemistry Core will also support oligonucleotides for Program 2 for footprinting studies; synthesis of specific oligonucleotides for Program 3 for probes for screening of clones; and production of compounds (small scale-up) for in vivo testing carried out in Program 4. Our general approach will be, first, to identify the most efficient synthetic route to the target compound using the synthetic knowledge of the chemistry staff and by searching the literature for known reactions which achieve the chemical transformations needed in the synthesis of the target. Our staff is trained in the use of on-line searching of STN International electronic databases such as Chemical Abstracts, Beilstein, and CAS REACT. Next, a time table will be drawn to assure that the compound can be prepared and characterized by the date required by the program leader. The synthetic route will be approved by the Core Leader and assigned to a synthetic chemist. The progress of the synthesis will be monitored weekly to insure progress is being made. Intermediates and final product will be fully characterized and purity determined using the analytical instrumentation located in-house and described in the analytical section. Strict guidelines will be adhered to in the quality of product prepared for the NCDDG. Final product will be submitted to the Program Leader with a written report indicating the synthetic route followed and the analytical data generated to characterize the compound and determine its purity.